Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation

BACKGROUND. Cytokines are key mediators of inflammation that may relate to prostate cancer initiation and progression, and that may be useful markers of prostatic neoplasia and related inflammation. In order to better understand the relationship between cytokines and prostate cancer, we profiled cytokines in prostatic fluids obtained from cancerous prostate glands and correlated them to both cancer status and inflammatory grade. METHODS. Prostatic fluid was collected from fresh radical prostatectomy specimens and analyzed by cytokine antibody microarray. For comparison, cases were selected from patients with either minimal or extensive cancer volume on final pathology. Among the cytokines with the greatest difference between the tumor volume groups, eight had their levels quantitated by ELISA. In addition, the grade of prostatic inflammation by neutrophils, macrophages and lymphocytes was scored for each case and examined for correlations with cytokine levels. RESULTS. Among 174 cytokines analyzed, HGF was the most increased (6.57-fold), and along with IL18Bpa was significantly elevated in patients with extensive disease compared to those with minimal disease. IL17, GITR, and ICAM-1 were elevated in specimens with significant neutrophilic inflammation into gland lumina, and IL18Bpa, IL17, GITR, and ICAM-1 were elevated in specimens with significant lymphocytic inflammation in prostatic stroma. CONCLUSIONS. Prostatic fluid cytokines were identified that may be useful for early cancer detection and prognostication efforts and for assessment of prostatic inflammation, particularly if they can be found not only in prostatic fluids obtained ex vivo, but in expressed prostatic secretions or urine samples from men with prostates still in situ.